VRK2_MOUSE
ID VRK2_MOUSE Reviewed; 503 AA.
AC Q8BN21; Q3U415; Q5F1Z5; Q5SP88; Q8BPU8; Q8CJ46; Q91WS1; Q9CZF9;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Serine/threonine-protein kinase VRK2;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q86Y07};
DE AltName: Full=Vaccinia-related kinase 2;
GN Name=Vrk2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J;
RX PubMed=12417526; DOI=10.1093/hmg/11.24.3047;
RA Agoulnik A.I., Lu B., Zhu Q., Truong C., Ty M.T., Arango N., Chada K.K.,
RA Bishop C.E.;
RT "A novel gene, Pog, is necessary for primordial germ cell proliferation in
RT the mouse and underlies the germ cell deficient mutation, gcd.";
RL Hum. Mol. Genet. 11:3047-3053(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Dendritic cell, Embryo, Eye, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=12782311; DOI=10.1016/s0014-5793(03)00501-5;
RA Vega F.M., Gonzalo P., Gaspar M.L., Lazo P.A.;
RT "Expression of the VRK (vaccinia-related kinase) gene family of p53
RT regulators in murine hematopoietic development.";
RL FEBS Lett. 544:176-180(2003).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND AUTOPHOSPHORYLATION.
RX PubMed=14645249; DOI=10.1074/jbc.m310813200;
RA Nichols R.J., Traktman P.;
RT "Characterization of three paralogous members of the Mammalian vaccinia
RT related kinase family.";
RL J. Biol. Chem. 279:7934-7946(2004).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=31142202; DOI=10.1080/19491034.2019.1618175;
RA Cheng L.C., Baboo S., Lindsay C., Brusman L., Martinez-Bartolome S.,
RA Tapia O., Zhang X., Yates J.R. III, Gerace L.;
RT "Identification of new transmembrane proteins concentrated at the nuclear
RT envelope using organellar proteomics of mesenchymal cells.";
RL Nucleus 10:126-143(2019).
CC -!- FUNCTION: Serine/threonine kinase that regulates several signal
CC transduction pathways (PubMed:14645249). Modulates the stress response
CC to hypoxia and cytokines, such as interleukin-1 beta (IL1B) and this is
CC dependent on its interaction with MAPK8IP1, which assembles mitogen-
CC activated protein kinase (MAPK) complexes (By similarity). Inhibition
CC of signal transmission mediated by the assembly of MAPK8IP1-MAPK
CC complexes reduces JNK phosphorylation and JUN-dependent transcription
CC (By similarity). Phosphorylates histone H3 (By similarity).
CC Phosphorylates 'Thr-18' of p53/TP53, and thereby increases its
CC stability and activity (By similarity). Phosphorylates BANF1 and
CC disrupts its ability to bind DNA and reduces its binding to LEM domain-
CC containing proteins (By similarity). Down-regulates the transactivation
CC of transcription induced by ERBB2, HRAS, BRAF, and MEK1 (By
CC similarity). Blocks the phosphorylation of ERK in response to ERBB2 and
CC HRAS (By similarity). May also phosphorylate MAPK8IP1 (By similarity).
CC Can also phosphorylate the following substrates that are commonly used
CC to establish in vitro kinase activity: casein, MBP and histone H2B, but
CC it is not sure that this is physiologically relevant (By similarity).
CC {ECO:0000250|UniProtKB:Q86Y07, ECO:0000269|PubMed:14645249}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:Q86Y07};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000250|UniProtKB:Q86Y07};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q86Y07};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC Evidence={ECO:0000250|UniProtKB:Q86Y07};
CC -!- SUBUNIT: Interacts with MAP3K7, MAP2K7, MAP2K1, KSR1, RAN and MAPK8IP1.
CC {ECO:0000250|UniProtKB:Q86Y07}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14645249}.
CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:31142202}; Single-
CC pass type IV membrane protein {ECO:0000255}. Mitochondrion membrane
CC {ECO:0000250|UniProtKB:Q86Y07}; Single-pass type IV membrane protein
CC {ECO:0000255}. Nucleus envelope {ECO:0000269|PubMed:31142202}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8BN21-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BN21-2; Sequence=VSP_008543;
CC Name=3;
CC IsoId=Q8BN21-3; Sequence=VSP_008541, VSP_008542;
CC -!- TISSUE SPECIFICITY: Expressed in liver, kidney and muscle. Weakly
CC expressed in thymus, bone marrow and spleen.
CC {ECO:0000269|PubMed:12782311}.
CC -!- DEVELOPMENTAL STAGE: Weakly expressed in embryo compared to VRK1 and
CC VRK3. Expressed from 10.5 dpc to 14 dpc in developing liver and then
CC decreases. It increases again from 17.5 dpc and remains thereafter.
CC Highly expressed in hematopoietic embryonic tissues from 10.5 dpc to
CC 14.5 dpc. Weakly expressed in the yolk-sac.
CC {ECO:0000269|PubMed:12782311}.
CC -!- PTM: Autophosphorylated. {ECO:0000269|PubMed:14645249}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr
CC protein kinase family. VRK subfamily. {ECO:0000305}.
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DR EMBL; AF513620; AAN64922.1; -; mRNA.
DR EMBL; AK012664; BAB28393.1; -; mRNA.
DR EMBL; AK053297; BAC35335.1; -; mRNA.
DR EMBL; AK154485; BAE32620.1; -; mRNA.
DR EMBL; AC083815; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL929272; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC013520; AAH13520.1; -; mRNA.
DR CCDS; CCDS24486.1; -. [Q8BN21-1]
DR RefSeq; NP_001239376.1; NM_001252447.1. [Q8BN21-2]
DR RefSeq; NP_081536.2; NM_027260.3. [Q8BN21-1]
DR RefSeq; XP_006514864.1; XM_006514801.3. [Q8BN21-1]
DR AlphaFoldDB; Q8BN21; -.
DR SMR; Q8BN21; -.
DR BioGRID; 213758; 5.
DR STRING; 10090.ENSMUSP00000077471; -.
DR iPTMnet; Q8BN21; -.
DR PhosphoSitePlus; Q8BN21; -.
DR EPD; Q8BN21; -.
DR jPOST; Q8BN21; -.
DR MaxQB; Q8BN21; -.
DR PaxDb; Q8BN21; -.
DR PeptideAtlas; Q8BN21; -.
DR PRIDE; Q8BN21; -.
DR ProteomicsDB; 299732; -. [Q8BN21-1]
DR ProteomicsDB; 299733; -. [Q8BN21-2]
DR ProteomicsDB; 299734; -. [Q8BN21-3]
DR Antibodypedia; 30474; 218 antibodies from 30 providers.
DR DNASU; 69922; -.
DR Ensembl; ENSMUST00000078362; ENSMUSP00000077471; ENSMUSG00000064090. [Q8BN21-1]
DR Ensembl; ENSMUST00000109504; ENSMUSP00000105130; ENSMUSG00000064090. [Q8BN21-1]
DR GeneID; 69922; -.
DR KEGG; mmu:69922; -.
DR UCSC; uc007igf.2; mouse. [Q8BN21-1]
DR UCSC; uc007igg.2; mouse. [Q8BN21-3]
DR UCSC; uc011xsk.2; mouse. [Q8BN21-2]
DR CTD; 7444; -.
DR MGI; MGI:1917172; Vrk2.
DR VEuPathDB; HostDB:ENSMUSG00000064090; -.
DR eggNOG; KOG1164; Eukaryota.
DR GeneTree; ENSGT00940000158042; -.
DR HOGENOM; CLU_019279_4_3_1; -.
DR InParanoid; Q8BN21; -.
DR OMA; YCESQIL; -.
DR OrthoDB; 866200at2759; -.
DR PhylomeDB; Q8BN21; -.
DR TreeFam; TF106473; -.
DR Reactome; R-MMU-2995383; Initiation of Nuclear Envelope (NE) Reformation.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013404; RAC2 GTPase cycle.
DR Reactome; R-MMU-9013405; RHOD GTPase cycle.
DR Reactome; R-MMU-9013408; RHOG GTPase cycle.
DR Reactome; R-MMU-9013423; RAC3 GTPase cycle.
DR BioGRID-ORCS; 69922; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Vrk2; mouse.
DR PRO; PR:Q8BN21; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8BN21; protein.
DR Bgee; ENSMUSG00000064090; Expressed in floor plate of midbrain and 196 other tissues.
DR ExpressionAtlas; Q8BN21; baseline and differential.
DR Genevisible; Q8BN21; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:MGI.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0016572; P:histone phosphorylation; IBA:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:2000659; P:regulation of interleukin-1-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0043408; P:regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cytoplasm; Endoplasmic reticulum;
KW Kinase; Membrane; Mitochondrion; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..503
FT /note="Serine/threonine-protein kinase VRK2"
FT /id="PRO_0000086807"
FT TRANSMEM 482..502
FT /note="Helical; Anchor for type IV membrane protein"
FT /evidence="ECO:0000255"
FT DOMAIN 29..313
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 334..353
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 362..395
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 392..503
FT /note="Interaction with MAP3K7"
FT /evidence="ECO:0000250|UniProtKB:Q86Y07"
FT COMPBIAS 362..379
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 166
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 35..43
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 61
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 336
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q86Y07"
FT VAR_SEQ 151..163
FT /note="LDVLEYIHENEYV -> VSLRDLTGDLLDI (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008541"
FT VAR_SEQ 164..503
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008542"
FT VAR_SEQ 342..390
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008543"
FT CONFLICT 33
FT /note="K -> R (in Ref. 1; AAN64922)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="A -> P (in Ref. 2; BAB28393)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="P -> L (in Ref. 2; BAE32620 and 4; AAH13520)"
FT /evidence="ECO:0000305"
FT CONFLICT 333
FT /note="H -> R (in Ref. 2; BAE32620 and 4; AAH13520)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 503 AA; 58119 MW; 6F29E3E412ECB221 CRC64;
MAPRRKEKYK LPVPLPEGKI LDDMEGNRWA LGKMIGSGGF GLIYLAFPTN KPNKDARHVI
KLEYQENGPL FSELKFYQRA AKRECIQKWI QQRKLDYLGI PVFYGFGLTD FKGRSYRFMV
MERLGIDLQK LLDQNGGFKK LTVLQLGIRM LDVLEYIHEN EYVHGDIKAA NLLLDFTNPD
RVYLADYGLS YRYCPNGNHK QYQEDPRKGH NGTIEFTSLD AHKGVAPSRR SDVEILGYCM
LHWLFGKLPW EAKLDDPVAV QTAKTNLLDE LPESVLKWAP SGSSCSELVK YLMYVHNLAY
DDKPDYQKLK KILNPDGVPL GPLEFSTKVQ SVHVRTPAQQ KVDSPKATRK PANEFPAKFP
KKVHRETRAR QREEQEDSQP TMLQSRPAAP ENSRTRKIHE YSDIFSEMQS LQQTPSYMSF
QGSYCKPYLD CTRRDPIRKP RSLPRYRHTP TGNLGVTDLE SSPRFWPAIF QLTLSEETKA
DVYYYGITIF CLLIFVFLAL YFL
